Achievement rate of target blood pressure in patients with hypertension treated by hypertension specialists and non-specialists in a real-world setting.

Hypertension remains a major global healthcare issue. Considering that most Japanese patients with hypertension are managed by general practitioners, hypertension specialists should be involved in actual clinical practice. We investigated the blood pressure (BP), guidelines recommended for achievement rate of the target BP, and clinical variables of patients with hypertension treated by hypertension specialists and those treated by non-specialists in a real-world setting. Factors associated with the target BP achievement in this population were also investigated. Outpatients with hypertension from 12 medical facilities in Okinawa Prefecture were enrolled (n = 1469 [specialist group, 794; non-specialist group, 675]; mean age, 64.2 years; females, 45.8%). For all patients, BP and rate of the target BP achievement were 129.0 ± 15.5/74.6 ± 10.6 mmHg, and 51.8%, respectively. BP and the rate of target of BP achievement were 128.0 ± 15.1/73.4 ± 10.4 mmHg and 56.7% in the specialist group, and they were 130.1 ± 15.9/76.0 ± 10.8 mmHg and 46.1% in the non-specialist group. The urinary salt excretion and obesity rates were comparable between the specialist and non-specialist groups. Multivariable logistic analyses indicated that hypertension specialists and good medication adherence were positive factors, whereas obesity, chronic kidney disease, diabetes mellitus, and urinary salt excretion were inverse factors associated with target BP achievement in this population. Initiatives for salt reduction, medication adherence, and proper obesity management are crucial to improving BP management in patients with hypertension. Hypertension specialists are expected to play an essential role in them. For all patients, the target blood pressure (BP) achievement rate were 51.8%. Hypertension specialists and good medication adherence were positive factors in achieving target BP; conversely, obesity, diabetes mellitus, chronic kidney disease, and high urinary salt excretion were inverse factors in achieving target BP among patients with hypertension.

Urate-lowering drugs for chronic kidney disease with asymptomatic hyperuricemia and hypertension: a randomized trial.

INTRODUCTION: Xanthine oxidase (XO) inhibitors may slow down chronic kidney disease (CKD) progression. The comparative effectiveness of the different urate-lowering drugs is unknown. The aim of this study was to determine whether urate-lowering therapy with an XO inhibitor (febuxostat) and that with a uricosuric drug (benzbromarone) are comparable in slowing renal function decline in patients with CKD complicated with hypertension and hyperuricemia. METHODS: This study was an open-label randomized parallel-group clinical trial of 95 patients with stage G3 CKD in Japan. The patients had hypertension and hyperuricemia without a history of gout. They were randomized to receive febuxostat ( n  = 47; febuxostat group) or benzbromarone ( n  = 48; benzbromarone group) and titrated to reduce their serum urate level to <6.0 mg/dl. The primary end-point was change in estimated glomerular filtration rate (eGFR) from baseline to 52 weeks. The secondary end-points included changes in uric acid level, blood pressure, urinary albumin-to-creatinine ratio, and XO activity. RESULTS: Of the 95 patients, 88 (92.6%) completed the trial. There were no significant differences in change in eGFR (in ml/min/1.73 m 2 ) between the febuxostat [-0.23, 95% confidence interval (CI), -2.00 to 1.55] and benzbromarone (-2.18, 95% CI, -3.84 to -0.52) groups (difference, 1.95; 95% CI, -0.48 to 4.38; P  = 0.115) nor in the secondary end-points, except for XO activity. Febuxostat significantly reduced XO activity ( P  = 0.010). There were no significant differences in primary and secondary outcomes between the groups. A decrease in eGFR was significantly less in the febuxostat group than that of the benzbromarone group in the CKDG3a, but not in CKDG3b, in the subgroup analysis. There were no adverse effects specific to either drug. CONCLUSIONS: No significant differences were found in the effects of febuxostat and benzbromarone in renal function decline in stage G3 CKD complicated with hyperuricemia and hypertension.

Salt and potassium intake evaluated with spot urine and brief questionnaires in combination with blood pressure control status in hypertensive outpatients in a real-world setting.

Reducing salt and increasing potassium intake are recommended lifestyle modifications for patients with hypertension. The estimated 24-h urinary salt excretion value from spot urine using Tanaka's formula and the salt check-sheet scores, questionnaire-based scores of salt intake, are practical indices of daily salt intake. However, few studies have evaluated salt intake with these methods in hypertensive outpatients. We examined salt and potassium intake with the spot urine method and the salt check-sheet scores of hypertensive outpatients in a multi-facility, real-world setting and examined whether the salt or potassium intake evaluated with these methods related to inadequate blood pressure control. Hypertensive outpatients from 12 medical facilities in the Okinawa prefecture were enrolled from November 2011 to April 2014 (n = 1559, mean age 63.9 years, 46% women). The mean blood pressure, urinary salt excretion value, urinary potassium excretion value, and total score on the salt check-sheet were 129/75 mmHg, 8.7 g/day, 1.6 g/day, and 10.4 points, respectively. The urinary salt excretion value and total score on the salt check-sheet but not urinary potassium excretion value were associated with inadequate blood pressure control (≥140/90 mmHg). Higher body mass index, estimated glomerular filtration rate, urinary potassium excretion value, total score on the salt check-sheet, and presence of inadequate blood pressure control were associated with high urinary salt excretion (≥10.2 g/day). In conclusion, hypertensive outpatients with high urinary salt excretion values estimated using Tanaka's formula or with high scores on the salt check sheet may be candidates for more intensive salt reduction guidance.

A questionnaire survey to assess lower urinary tract symptoms in patients with chronic stroke.

OBJECTIVES: In this study, we evaluated the prevalence of lower urinary tract symptoms and the associated clinical features in patients with chronic stroke. METHODS: Patients with stroke who had been regularly followed up at general medical hospitals in Okinawa, Japan were enrolled in the study. The patients were asked to complete a self-reported questionnaire regarding their physical activity, medical history, and the core lower urinary tract symptom score (CLSS) questionnaire, with anonymity. The association between each urinary disturbance category and the clinical characteristics of the patients such as age, gender, physical activity, and underlying disease was evaluated. RESULTS: In total, 51 patients (33 men and 18 women; mean age, 71.7 years) were eligible for analysis. The average time after the first stroke onset was 8.5 years. Nocturia and urgency incontinence had the greatest impact on the quality of life. Overactive bladder symptoms such as nocturia, urgency, urgency incontinence, and stress urinary incontinence were associated with age, female sex, and having a co-existing medical condition (such as ischemic heart disease, hypertension, and depression). Voiding symptoms such as slow stream and straining were associated with age and physical activity after stroke. CONCLUSIONS: Storage symptom is associated with not only neurological deficits but also sex and the presence of general diseases, whereas voiding symptom is influenced by physical activity in patients with chronic stroke. Therefore, lower urinary tract symptoms should be carefully monitored and physical rehabilitation should also be considered in patients with stroke.

Effects of xanthine oxidase inhibitors on renal function and blood pressure in hypertensive patients with hyperuricemia.

Hyperuricemia may promote the progression of hypertension and renal dysfunction. However, the effects of hyperuricemia treatment on blood pressure and renal function in adult hypertensive patients with hyperuricemia remain unclear. A total of 137 hypertensive patients with hyperuricemia (96 men and 41 women; mean age of 67 years) who recently started taking xanthine oxidase inhibitors (allopurinol or febuxostat) as outpatients were recruited. Serum uric acid level, estimated glomerular filtration rate (eGFR, ml min(-1) per 1.73 m(2)) and blood pressure (mm Hg) were retrospectively compared immediately before and shortly after starting treatment with xanthine oxidase inhibitors. The mean blood pressure and the eGFR immediately before starting treatment were 128/71 mm Hg and 44.6 ml min(-1) per 1.73 m(2), respectively. Although the eGFR decreased from 46.6 to 44.6 ml min(-1) per 1.73 m(2) before starting treatment with xanthine oxidase inhibitors, it increased to 46.2 ml min(-1) per 1.73 m(2) (P=0.001, compared with immediately before treatment) without any significant changes in blood pressure after the administration of xanthine oxidase inhibitors. Multiple regression analysis revealed that the increase in eGFR after starting xanthine oxidase inhibitor treatment positively correlated with the changes in systolic blood pressure and negatively correlated with the changes in uric acid levels and the use of renin-angiotensin system inhibitors. These results suggest that xanthine oxidase inhibitors may delay the progression of renal dysfunction in adult hypertensive patients with hyperuricemia.

Prevalence and Risk Factors for Nocturia in an Outpatient Clinic.

OBJECTIVES: We evaluated the prevalence of and risk factors in patients with nocturia at a general medical clinic in Naha, Japan. METHODS: We enrolled patients who had been regularly followed-up at a general medical clinic in Naha. Patients were asked to complete a self-reported questionnaire regarding medical history and the frequency of nocturnal voids in the last month with anonymity. Univariate and multivariate logistic regression tests were used to evaluate the risk factors for clinically significant nocturia. RESULTS: In total, 357 patients (men, 192; women, 165; mean age, 60 years) were eligible for analysis. The prevalence rate of clinically significant nocturia in patients was 33.8%. Univariate, as well as multivariate, analysis revealed that age, gender, and hypertension were significant risk factors for nocturia. CONCLUSION: Clinically significant nocturia is common among patients seen at a general medical clinic. Age and gender are the most definitive risk factors for nocturia. Hypertension may also be related to nocturia. Thus, it is important to evaluate not only urological problems but other medical problems in patients with nocturia.

Beneficial effect of switching from a combination of angiotensin II receptor blockers other than losartan and thiazides to a fixed dose of losartan/hydrochlorothiazide on uric acid metabolism in hypertensive patients.

Among the angiotensin II receptor blockers (ARBs), losartan (LOS) has uricosuric action. The clinical benefits of LOS compared with those of other ARBs may be apparent when it is combined with diuretics, which have an unfavorable influence on serum uric acid (SUA). The effects of switching from combinations of ARBs other than LOS and thiazides to a fixed-dose combination comprising 50 mg LOS and 12.5 mg hydrochlorothiazide on blood pressure (BP), SUA, percent fractional excretion of UA (FEUA), and urine pH were assessed in 57 hypertensive outpatients. A significant reduction in BP was observed after 6 months (P < .01). The switching therapy significantly decreased SUA level (6.0 ± 1.3 vs. 5.7 ± 1.3 mg/dL, P < .01), which was accompanied by increases in FEUA (P < .01) and urine pH (P < .01). The change in SUA was negatively correlated with the changes in FEUA (P < .004) and estimated glomerular filtration rate (P < .05). The change in FEUA was positively correlated with the changes in urine pH (P < .05) but not with BP or estimated glomerular filtration rate. In a separate group of patients treated with ARBs other than LOS (n = 82), a significant BP reduction was observed, but no change in SUA or FEUA was observed. In conclusion, switching therapy decreased SUA level, which was accompanied by an increase in FEUA. This result may depend on the balance between LOS-induced inhibitory action of urate transporter 1 and hydrochlorothiazide-induced plasma volume reduction. The increase in urine pH plays a role in UA urinary excretion.

Switching therapy from variable-dose multiple pill to fixed-dose single-pill combinations of angiotensin II receptor blockers and thiazides for hypertension.

The efficacy and tolerability of switching therapy from free combinations of angiotensin II receptor blocker (ARB) and thiazide (A/T) to a fixed-dose of losartan and hydrochlorothiazide (L/H) has not been evaluated in Japan. We examined effects of switching therapy from variable-dose multiple-pill A/T to a fixed-dose L/H on blood pressure (BP) along with medication adherence and the degree of satisfaction in 91 hypertensive outpatients (mean age, 65.2 ± 9.6 years). After 6 months, a significant BP reduction (132 ± 9/76 ± 10 vs. 126 ± 12/72 ± 11 mm Hg), along with an improvement of attaining target BP (44.0 vs. 61.5%) and that of adherence, were observed. The magnitude of BP reduction in the participants increased their degree of satisfaction more significantly than in the participants who worsened their degree of satisfaction. The estimated glomerular filtration rate and the serum uric acid (UA) level decreased slightly but significantly. The hemoglobin A1c of participants with diabetes mellitus increased slightly but significantly. In conclusion, a switch in therapy from variable-dose, multiple-pill A/T combinations to a fixed-dose, single-pill L/H was effective in decreasing BP and serum UA in Japanese clinical practice. Metabolic side effects of L/H in patients with diabetes mellitus remain to be investigated.

Penicillin G-induced hemorrhagic cystitis with hydronephrosis.

Irritable urological symptoms with gross hematuria and bilateral lumbar pain developed when the patient received penicillin G for endocarditis. These symptoms were followed by renal insufficiency. A contrast-enhanced abdominal computed tomography (CT) scan revealed a thickened bladder wall, bilateral hydroureter and hydronephrosis, suggesting hemorrhagic cystitis complicated with urinary tract obstruction. Urine culture was negative. After discontinuation of penicillin G, all symptoms subsided and renal function recovered; hence, penicillin G seems to have been associated with hemorrhagic cystitis and acute kidney injury. Positive findings in the drug lymphocyte stimulation test (DLST) for penicillin G were consistent with this diagnosis.

Role of HCN4 channel in preventing ventricular arrhythmia.

Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the splice donor site of the HCN4 gene in a patient with idiopathic ventricular tachycardia, which was supposed to generate a truncated channel. To investigate the role of the HCN4 channel in ventricular arrhythmia, we introduced a ventricular action potential of I(f) channel produced by HCN4 in a computer simulation model and found that the I(f) channel generated a leaky outward current during the plateau phase of ventricular action potential. Currents through the I(f) channel were suggested to contribute to the shortening of the action potential duration and the prevention of early after-depolarization in bradycardia. These observations suggested that the HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.

Severe abdominal pain associated with allergic reaction to nafamostat mesilate in a chronic hemodialysis patient.

A 33-year-old woman was referred from an outside dialysis clinic to our hospital because of severe abdominal pain during hemodialysis. She had been on chronic hemodialysis for the past 11 years due to chronic glomerulonephritis. Nafamostat mesilate was used as an anticoagulant for hemodialysis, because it was during her menstrual period with hypermenorrhea. On admission, she had no abdominal pain or gynecological abnormalities. On the second day, she had similar abdominal pain during hemodialysis with nafamostat mesilate in our dialysis unit. The abdominal pain disappeared within 60 minutes after discontinuing the hemodialysis. We re-started dialysis using heparin instead of nafamostat mesilate and she had no symptoms. The titer of total immunoglobulin E was high. The drug lymphocyte stimulation test was positive for nafamostat mesilate and antigen specific immunoglobulin E to nafamostat mesilate was highly positive in her blood. Although an allergic reaction to nafamostat mesilate is a rare complication, it should be one of the differential diagnoses of abdominal pain occurring during hemodialysis.

Evidence for elevated pulse pressure in patients on chronic hemodialysis: a case-control study.

BACKGROUND: Few analyses have compared pulse pressure (PP) values in hemodialysis patients with healthy individuals, and they have provided only limited data. We retrospectively examined PP in a large cohort of hemodialysis patients and healthy control subjects. METHODS: The relationships of systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP to mean arterial pressure (MAP) levels were investigated in 234 chronic hemodialysis patients and in 682 control subjects matched for age, sex, diabetes mellitus, and body mass index. RESULTS: In both control and patients, PP was positively correlated with MAP, and the two regression lines were parallel (beta of control subjects = 0.52; beta of hemodialysis patients = 0.57, P = 0.48). According to the regression line, at any MAP level, the PP in hemodialysis patients was significantly higher than that in control subjects: the mean PP difference between control and patients was 19.2 mm Hg (95% CI, 17.2 to 21.1 mm Hg, P < 0.0001). When the relationships between MAP and SBP and that between MAP and DBP were analyzed, the regression lines were also parallel. However, at any MAP level, SBP was higher and DBP was lower in hemodialysis patients than control subjects; the mean SBP difference was 12.8 mm Hg (95% CI, 11.5 to 14.1 mm Hg, P < 0.0001) and mean DBP difference was 6.4 mm Hg (95% CI, 5.7 to 7.0 mm Hg, P < 0.0001). CONCLUSIONS: At any MAP level, hemodialysis patients had a higher SBP, lower DBP, and higher PP values than those control subjects with a normal renal function who were matched for age, sex, diabetes mellitus, and body mass index. Further study is needed to determine whether preventing or reducing an elevated PP improves the prognosis for hemodialysis patients.

Analysis of drug prescription in chronic haemodialysis patients.

BACKGROUND: Information concerning medication use in Asian haemodialysis patients is sparse. We surveyed prescribed medications and examined the relation between the number of medications and mortality and clinical characteristics in chronic haemodialysis patients, in Okinawa, Japan. METHODS: We conducted a cross-sectional multicentre survey in August 1999 and patients were observed during 13 months of follow up. RESULTS: The clinical demographics of 850 chronic haemodialysis patients in seven dialysis units were obtained. Compared with the mean number of medications prescribed in ambulatory patients treated in general practice reported from Ministry of Health and Welfare of Japan (2.7 (n=20 716)), the mean number medications in haemodialysis patients was larger (7.2 (n=850)). The three most prescribed drug types in haemodialysis patients were those related to calcium and phosphate metabolism (88%), antihypertensive agents (71%), and erythropoietin (60%). Among the 850 patients, 38 died during the 13-month follow-up period. The number of medications was positively associated with mortality after adjusting for age, sex, and other clinical factors: the hazard ratio was 1.14 (95% confidence interval 1.03-1.26, P=0.007). A multiple linear regression analysis using the number of medications as a dependent factor and sex and other clinical characteristics as independent factors revealed that male sex (P=0.04), diabetes mellitus (P<0.0001), and duplication of drugs (P<0.0001) were positively correlated with the number of medications. CONCLUSIONS: Multiple drug use was observed in haemodialysis patients. The number of prescribed drugs was a significant predictor of short-term mortality. Male sex, diabetes mellitus, and duplication of drugs were correlated with increases in the number of medications.

End-stage renal disease associated with familial Mediterranean fever.

A 39-year-old man had been suffering from periodic fever since childhood. He was started on hemodialysis due to secondary amyloidosis on December 2000. The patient was believed to have Familial Mediterranean fever (FMF) because of recurrent fever with peritonitis, arthritis and inflammatory changes and secondary amyloidosis in his kidneys, heart and colon. No other family member had recurrent fever. IL-6, TNF, and dopamine beta-hydroxylase were not increased in the febril phase. The patient was homozygous for the M6941 mutation. We report the first Japanese case of FMF associated with amyloidosis and confirmed by a gene mutation.

A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings.

A 40-year-old woman was referred for several episodes of coma lasting from 2 hours to 2 days. She had been on maintenance hemodialysis for polycystic kidney disease for 9 months. Laboratory findings showed high serum levels of ammonia and citrulline, and a diagnosis of adult-onset type II citrullinemia was made. Multiple areas of focal brain edema were shown by magnetic resonance imaging. The clinical manifestations of coma and abnormal behavior were resolved with intensified dialysis (ie, four 5-hour sessions per week with glycerol and continuous ambulatory peritoneal dialysis). No abnormal shadow was present on follow-up magnetic resonance imaging. Such intensified dialysis therapy may be effective for adult-onset type II citrullinemia and may be applicable even in patients who do not have end-stage renal disease if liver transplant is not an option.

[A case of hemodynamic brain infarction with postprandial hypotension].

A 76-year-old man with left internal carotid artery occlusion developed a progressing right hemiparesis. Brain MRI presented reinfarctions in the left anterior border zone and terminal zone in the left deep white matter. Ambulatory blood pressure monitoring showed a decrease in systolic blood pressure by more than 20 mmHg one hour after starting meals, which is considered as postprandial hypotension. The recurrent stroke occurred probably by a hemodynamic mechanism with the presence of internal carotid artery occlusion and postprandial hypotension. Administration of voglibose, an alpha-glucosidase inhibitor, improved postprandial hypotension. In patients with severe carotid or intracranial artery disease, the postprandial hypotension should be carefully monitored for prevention of hemodynamic brain ischemia.